Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol.

Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Research Abstract Details 

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Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Abstract Text:

Abed N Azab,Quan He,Shulin Ju,Guiling Li,Miriam L Greenberg,

Studies have shown that the inositol biosynthetic pathway and the enzyme glycogen synthase kinase-3 (GSK-3) are targets of the mood-stabilizing drugs lithium and valproate. However, a relationship between these targets has not been previously described. We hypothesized that GSK-3 may play a role in inositol synthesis, and that loss of GSK-3 may lead to inositol depletion, thus providing a mechanistic link between the two drug targets. Utilizing a yeast Saccharomyces cerevisiae gsk-3Delta quadruple-null mutant, in which all four genes encoding homologues of mammalian GSK-3 are disrupted, we tested the hypothesis that GSK-3 is required for de novo inositol biosynthesis. The gsk-3Delta mutant exhibited multiple features of inositol depletion, including defective growth in inositol-lacking medium, decreased intracellular inositol, increased INO1 and ITR1 expression, and decreased levels of phosphatidylinositol. Treatment of wild-type cells with a highly specific GSK-3 inhibitor led to a significant increase in INO1 expression. Supplementation with inositol alleviated the temperature sensitivity of gsk-3Delta. Activity of myo-inositol-3 phosphate synthase, the rate-limiting enzyme in inositol de novo biosynthesis, was decreased in gsk-3Delta. These results demonstrate for the first time that GSK-3 is required for optimal myo-inositol-3 phosphate synthase activity and de novo inositol biosynthesis, and that loss of GSK-3 activity causes inositol depletion.

Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Publishing Authors By Initials

AN Azab,Q He,S Ju,G Li,ML Greenberg,

For similar thiazoles: thiadiazoles research abstracts see: thiazoles: thiadiazoles research

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Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular microbiology

VOLUME: 63

Page Numbers: 1248-58

Journal Abbreviation: Mol. Microbiol.

ISSN: 0950-382X

DAY: 3

MONTH: Feb

YEAR: 2007

Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8712028

Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Keywords Mesh Terms:

KEYWORDS: Thiadiazoles

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol. Information

Substance Name: Myo-Inositol-1-Phosphate Synthase

Registry Number: EC 5.5.1.4

Grant and Affiliation Information for Glycogen synthase kinase-3 is required for optimal de novo synthesis of inositol.

AFFILIATION: Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.

Country: England

AGENCY: United States NIMH

GRANT: MH 56220

ACRONYM: MH

MEDLINETA: Mol Microbiol

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